Inhibition of Fas/FasL mRNA expression and TNF-alpha release in concanavalin A-induced liver injury in mice by bicyclol

Abstract

Aim: Bicyclol, 4, 4'-dimethoxy-5, 6, 5', 6'-dimethylene-dioxy-2-hydroxymethyl -2'-carbonyl biphenyl, is a new anti-hepatitis drug. The aim of the present study was to investigate the protective effect of bicyclol on concanavalin A (Con A)-induced immunological liver injury in mice and its mechanism.

Methods: Liver injury was induced by injection of Con A via tail vein of mice and assessed biochemically and histologically. Serum transaminase and tumor necrosis factor alpha (TNF-alpha) were determined. Liver lesions were observed by light microscope. Expressions of TNF-alpha, interferon gamma (IFN-gamma), Fas and Fas ligand (FasL) mRNA in the livers were measured by RT-PCR.

Results: Serum transaminase level and liver lesions in Con A-induced mice were markedly reduced by oral administration of 100, 200 mg/kg of bicyclol. TNF-alpha level in serum was also reduced by bicyclol. Con A injection induced up-regulation of TNF-alpha, IFN-gamma, Fas and FasL mRNA expression in liver tissues. Bicyclol significantly down-regulated the expression of IFN-gamma, Fas and FasL mRNA, but only slightly affected TNF-alpha mRNA expression in liver tissues.

Conclusion: Bicyclol protects against Con A-induced liver injury mainly through inhibition of Fas/FasL mRNA expression in liver tissues and TNF-alpha release in mice.

Figure 1

Chemical structure of bicyclol.

Figure 2

Time-course of Con A-induced liver serum ALT el-evation in mice. ^bP < 0.01 vs other time.

Figure 3

Light micrographs of livers from mice treated with Con A alone or in combination with bicyclol. Original magnification×200. A: normal control mouse. B: Con A injected mouse; C, mouse treated with bicyclol 200 mg/kg.

Figure 4

Dynamic changes of serum TNF-α level after Con A injection in mice. Each point represents mean ± SD of six mice.

Figure 5

Lowering effect of bicyclol on the elevated serum TNF-α Level induced by Con A injection in mice. Each bar represents mean ± SD of 6 mice per group ^bP < 0.01 vs Con A alone.

Figure 6

Effect of bicyclol on Con A induced TNF-α, IFN-γ, Fas and FasL mRNA expression determined by RT-PCR. A: Pho-tograph of ethidium bromide-stained amplification products. Lane 1, molecular mass markers; lane 2 and lane 3, control liver; lane 4 and lane 5, liver 2 h after Con A administration alone; lane 6 and lane 7, liver 2 h after injection of Con A in combination with 200 mg/kg bicyclol. B: Relative band intensity of amplification products compared with Cu/Zn SOD mRNA. Data represent the mean of two lanes. Each lane corresponds to the pooled livers from two mice. ^aP < 0.05 vs Con A alone.